This is Steven Salzberg's blog on genomics, pseudoscience, medical breakthroughs, higher education, and other topics, including skepticism about unscientific medical practices. Here's where I can say what I really think about abuses and distortions of science, wherever I see them.

Do hyaluronic acid injections help knee pain? Don't waste your money.

As spring turns into summer, we spend more time outdoors, exercising, gardening, or just walking around. And for many people, more exercise means knee pain. Count me among the afflicted.

Several people, including my orthopedic specialist, have suggested that I try injections of hyaluronic acid to treat my knee pain. Many people swear by it, and even though I looked into this two years ago (and rejected it as ineffective), I thought I would look again. Perhaps the evidence had changed.

It hadn't.

Superficially, these injections sound reasonable. Hyaluronic acid is already inside your knee and helps to lubricate and cushion the joint. Adding more lubricant seems like a good idea; after all, it works for cars, bicycles, door hinges, or any other creaky joint.

But not for knees. Just recently, Anne Rutjes, Peter Jüni and their colleagues published a very large review of the evidence on knee injections. They looked at 89 trials involving over 12,000 adults and found that in the trials that were properly controlled (blinded), hyaluronic acid injections had either no effect or a “clinically irrelevant effect”; that is, too small a difference to matter to the patient. (They also found five unpublished trials that showed no effect at all; this is a good example of the so-called “file drawer effect”, where studies that don’t have the desired outcome are stashed away in a drawer and never published.)

Rutjes and colleagues also pointed out that there’s a real risk of harm when you inject something deep into the knee joint. To quote their summary for patients (published along with the article),

“Viscosupplementation [injection of hyaluronic acid] may provide little if no pain relief or function improvement in patients with knee osteoarthritis. It also seems to increase the risk for adverse events."

“We cannot recommend using hyaluronic acid for patients with symptomatic osteoarthritis of the knee. Strength of recommendation: Strong.”

After looking at numerous studies, the AAOS concluded that there was no clinically meaningful benefit from these injections. This document is their official recommendation for physicians.

I was disturbed, though, to find that the AAOS information for patients directly contradicts their own recommendations to clinicians, and suggests that knee injections might work. On their patient-oriented web page, they offer the wishy-washy comment that “hyaluronic acid does seem to have anti-inflammatory and pain-relieving properties … [that] may last for several months,” though “not all patients will have relief of pain.”

What the heck? Are they orthopedists trying to hide the truth from their patients? Why would they do that?

I checked to see if the AAOS patient information was merely out of date, but no, it was reviewed in 2014, and the clinical recommendations appeared in 2013. I have to assume that the authors of the patient information page are not the same doctors who established the official recommendations for clinicians–but it seems unlikely that they are ignorant of their own organizations official guidelines. So why don’t they warn patients that hyaluronic acid injections don’t work? Is it because hyaluronic acid treatments are a significant money-maker for some orthopedists?

I can hear the response from some doctors already: "In my experience," they say, "this works for some patients." Sorry, but one doctor's experience (or "clinical judgment", as some call it) doesn't trump science. That's why we do experiments, to determine whether or not our subjective impression is correct. In this case, the science is clear.

Incidentally, the Mayo Clinic also fails on this topic. Their site states that hyaluronic acid

“can be injected into your knee to improve mobility and ease pain. Relief may last as long as six months to a year.”

They cite no evidence to back this up. Patients looking at either the Mayo site or the AAOS site will be misled into thinking that these injections might be worth a try.

“one study published in Rheumatology found that hyaluronan was no better at reducing joint pain than a placebo injection of salt water. An analysis of seven different studies published in the Journal of Family Practice did not recommend the treatment, since the benefits–if it had any at all–were so slight.”

So what does work for knee pain? Physical therapy and exercise to strengthen the muscles around the knee is still the best course, according to the AAOS's clinical guide. Weight loss also helps, by reducing the load on the knee. The only medical intervention that helps is an NSAID pain reliever such as ibuprofen. (See my 2013 article for other treatments that don’t work, including acupuncture (not even close) and glucosamine-condroitin supplements).

As for me, I bought a knee brace even though the AAOS says it doesn’t help. But it feels like it’s helping, and it was cheap. And my knee is definitely feeling better. Why not take advantage of a placebo effect once in a while?